Abstract There is an urgent need for new diagnostic approaches for early identification and progression in Alzheimer?s disease (AD) and related dementias (ADRD). NIA?s Strategic Direction C and D to improve our understanding and develop interventions for mild cognitive impairment (MCI), the prodrome of AD. This proposal focuses on sleep status, a known hallmark of neurological disease, and commonly present in MCI/AD. Sleep disorder is associated with sleep deprivation (SD) from chronic sleep fragmentation or wake after sleep onset [WASO], poor sleep quality, etc. and clinically significant daytime cognitive decline. Activas Diagnostics (Activas-Diagnostics.com) offers a home-based, nonwearable, mattress-based sleep system, SleepMove, developed in clinical research and now is a patented biotechnology. Our sensor system provides standard actigraphy-type sleep fragmentation indices with the value proposition that SleepMove mattress platform identifies high frequency, sleep-related movement arousals (i.e. no EEg change, [MA]). As part of arousal neurocircuitry, MAs are deficient in sleep disorder and neurological disease. Our previous work has shown that MAs are sleep-related movement (SM) bursts (5-25 sec) that are periodic (2- 5 min) within the window of asphyxiation. It is known that SD suppresses the arousal system during sleep. Published work with the SleepMove system has established that MAs are similarly reduced by SD and significantly reduced in patients with neurological conditions. In a SleepMove pilot study, demographic control participants without SD (age 65-85) showed MAs that were robust, and triggered an increase in respiratory rate (termed SM-RR coupling). In contrast, MCI patients showed more SD and sleep fragmentation, as well as deficient MA vigor, and fewer and less efficient SM-RR coupling. SM-RR coupling supports respiratory tone, airway patency, and may moderate hypoxia risk during sleep. The design of the SleepMove mattress device integrates cutting-edge sensor technology, signal processing and statistical inference software to identify 2 distinct signature biomarkers of SD that complement standard actigraphy, and adds a novel parameter of respiratory function and modulation during sleep, long implicated in neurological decline. MA measured through SM (i.e. periodicity, patterning, and amplitude) and reflecting arousal tone, sleep fragmentation and SD; RR modulation through SM-RR coupling, a time series segmentation analysis of respiratory variability linked to MAs. In the proposed home-based clinical study, SD and cognitive decline (as parameters of MCI severity) will be estimated in diagnosed MCI and control participants from SleepMove actigraphy and new SD indicators: SM reduction, and poor responsiveness of RR during SM-RR coupling MA events. These novel physiological parameters are proposed correlates of poor sleep. To evaluate SleepMove predictive parameters, an overnight memory consolidation test of 10 min pre- vs. post-sleep (episodic and procedural) memory consolidation testing followed by complete neuropsychological battery within 30 days. MCI-diagnosed group will be compared to a demographic, nonMCI comparison group (N=100, age 65-85 years) referred from two gerontology and aging centers participating in this study. Participants living independently will be tested in the home with the Activas Diagnostics SleepMove mattress device for 7 nights to collect SM and respiratory (RR) time series, and standard actigraphy measures of sleep quality. On night 2, memory consolidation will be probed using a 5- min, automated pre-post sleep, brief memory app designed for easy, home use in cognitively challenged participants. Sleep and memory data will be collected and transmitted wirelessly to the lab for analysis with our proprietary algorithms. New diagnostic criteria for MCI and severity status will be developed using thresholding methods with ROC (receiver operating characteristics) statistical method comparing sleep health (i.e. SM, SM-RR coupling, sleep fragmentation and efficiency estimates) and sleep diary to the memory consolidation probe and neurocognitive battery. In a parallel stream, our commercialization effort will pursue appropriate professional staff to develop FDA and other regulatory solutions for ICD-10 designation and insurance adoption; develop new strategic partnering in the medical device-sleep business insurance community; and for business model scale up for Phase II goals. Future applications include investigations of AD related dementias and other neurological disease.